We are investigating gene expression in nervous tissue, using as tools steroid hormones which regulate pituitary function and influence behavior by interacting directly with the nervous system. Our approach emphasizes the fate of the hormones themselves: entry into the brain, intracellular conversion to more or less active metabolites; binding to soluble intracellular receptors; and transfer to the cell nucleus. We are also investigating the mediation by steroid receptor mechanisms of hormone-induced changes in enzyme activities, in an attempt to establish mechanisms by which gene expression can influence neural activity. In all of these studies, autoradiography an a variety of neurochemical and cell biological techniques are being employed. Another major action of steroid homones, especially of the gonadal steroids, on brain function is the influence on development. We are particularly interested in the receptor mechanisms responsible for sexual differentiation of the rat brain and are studying the possible involvement of estrogen receptors in this process. Autoradiography, neurochemical methods, and some behavioral measures are being employed in these studies.